Population HLA frequencies belong upstream of serial marker interpretation

High-resolution HLA frequency studies can inform donor and recipient genetic context, but population reference data alone do not establish how a rejection marker should be interpreted at a given sample time. Their contribution should be tested upstream: estimate genetic susceptibility, then ask whether it changes calibration of serial donor-derived cell-free DNA after accounting for time since transplant, prior values, contemporaneous graft injury, and treatment. Untreated rises and post-treatment declines require separate analyses. Apparent genetic effects could otherwise reflect population structure, baseline graft risk, or differences in when injury is sampled rather than added discrimination between rejection and non-rejection injury.